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E J Hammond

Publications and source records attributed to E J Hammond.

At least 19 recordsLinked to original sources

Neurochemical effects of vagus nerve stimulation in humans.

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.

Adult

Absence of cortical white matter changes in three patients undergoing long-term vigabatrin therapy.

Chronic administration of the experimental antiepileptic drug vigabatrin (gamma-vinyl GABA) to animals has been shown to cause dose-dependent neuropathological changes characterized by a microvacuolation in specific white matter tracts. This finding has led to some concern as to whether similar pathologic changes might occur in patients taking this medication. Here we report on analysis of tissue specimens taken during neurosurgery from three patients undergoing chronic vigabatrin therapy (4 g/day). The first patient, a 34-year-old woman, had taken vigabatrin for 2 years prior to surgery, the second, a 50-year-old man, had taken the drug for 1 year, and a 34-year-old man had taken the drug for 5.3 years. For comparison, similar specimens were taken from three other patients not taking vigabatrin who were undergoing surgery for intractable epilepsy. Specimens from each subject were prepared in an identical manner and examined with light and electron microscopy. All specimens were examined in a blinded fashion. There was some minor nonspecific myelinic splitting seen in both controls and vigabatrin-treated patients but there was no evidence for any drug-induced lesions similar to that seen in experimental animals.

Adult

Vagal stimulation for control of complex partial seizures in medically refractory epileptic patients.

Chronic intermittent stimulation of the vagus nerve is a new method currently being tested for the treatment of medically intractable complex partial seizures (CPS). We have studied the effects of vagal stimulation in nine patients with CPS for 4-16 months to determine its safety and efficacy. With the patients maintained on constant dosages of antiepileptic drugs, we recorded the electroencephalogram and electrocardiogram, and performed clinical laboratory tests and gastric analysis over a 6-week baseline period. The neurocybernetic prosthesis (NCP) was then implanted and connected to two spiral electrodes wound around the left vagus nerve. After a 4-week placebo period, vagal stimulation was started. Stimulation parameters were increased stepwise at monthly intervals until patients were being stimulated for 30-second periods at 20-50 Hz with 1-2 mA of current at 250-500 microseconds pulses. A second 4-week placebo period was added 3 months after the implantation. Thereafter, vagal stimulation was resumed and self-stimulation with magnetic activation was allowed for a 1-minute period at the onset of an aura. Six patients had a significant reduction in the frequency, intensity, or duration of seizures. All patients tolerated the implantation and stimulation well and none reported pain, discomfort, or important changes in their daily activities, sleep habits, eating, swallowing, or breathing. There were no remarkable changes in blood pressure or heart rate.

Adult

Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures.

A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire-electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow-up period make this a pilot study, but the results are promising.

Adult

Vagus nerve stimulation in humans: neurophysiological studies and electrophysiological monitoring.

Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus-nerve-evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 microV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep.

Adult

Cholinergic and serotonergic effects on the P3 potential and recent memory.

The effects of scopolamine (anticholinergic) and methysergide (antiserotonergic) on memory and long-latency auditory cognitive evoked potentials (EPs) were tested in 16 normal adults. Recent memory was impaired by both drugs. In contrast, scopolamine, but not methysergide, significantly delayed P3 latency and decreased P3 amplitude. Immediate memory and the earlier EP components (i.e., N1 and P2) were unaffected. The findings support the hypothesis that cholinergic neurons are important in the neuronal networks generating the P3 potential. Serotonergic neurons do not appear to play a major role in the networks that generate the P3.

Adult

Neuropharmacology of zonisamide, a new antiepileptic drug.

Zonisamide readily crosses the blood-brain barrier and is readily absorbed after oral administration with a Tmax of about 3 hr. The half-life of ZNA in epileptic patients is about 28 hr. Zonisamide has a broader therapeutic range than other antiepileptic drugs. Neurotoxic, hemapoietic, renal, and liver effects have been minimal in patients participating in controlled clinical studies. It is effective in several experimental models of epilepsy and in initial clinical trials has been shown to be effective in generalized tonic-clonic, simple, and complex partial seizures.

Animals

Prolonged survival of cultured keratinocyte allografts in the nonimmunosuppressed mouse.

The effect of in vitro culture on the survival of allografts of epidermal keratinocytes has been examined using a mouse model. Female BALB/c tail epidermal cells were cultured from single cell suspensions to form confluent sheets that were grafted onto male CBA recipients using a transplantation technique that ensured separation of donor graft from host skin. Animals were killed at defined intervals, and the status of the grafts determined histologically. Full thickness skin allografts rejected at 13-15 days. Allografts of epidermis (obtained by enzymatic cleavage at the dermoepidermal junction) rejected at 19-20 days. Cultured keratinocyte allografts were not rejected at least within 70 days and had a histological appearance identical to syngeneic controls. The expression of MHC class I and class II determinants and the leukocyte common (Ly5) surface marker on the donor cells before and after culture were examined using indirect immunofluorescence and monoclonal antibodies. These and other cytochemical studies showed that freshly dissociated tail epidermal cells contained 0.3% of cells that expressed membrane-bound ATP-ase activity, Ia antigens, and the Ly5 surface antigen. These are the Langerhans' cells of the epidermis. In culture, these cells decrease so that by day 8 of culture, no such cells can be detected. At confluence, there are no Ia positive cells, but all cells express MHC class I antigens and stain with an antikeratin antibody. The loss of Ia expression on culture correlates with a decreased stimulation of the class II H-2d-restricted T cell clone D7.1 by cultured keratinocytes compared with freshly dispersed epidermal cells. Furthermore, cultured keratinocytes fail to prime allogeneic mice as determined by the survival of whole thickness skin grafts, whereas freshly dispersed cells induce an accelerated rejection. The results suggest that the survival of cultured keratinocyte allografts is due to the elimination of cells expressing Ia antigens and supports the passenger leukocyte theory of graft rejection.

Animals

Cholinergic modulation of human P3 event-related potentials.

A paradigm for studying relations between behavioral, neurochemical, and electrophysiologic processes is presented. Scopolamine, a centrally acting anticholinergic agent, abolished the human auditory P3 event-related potential, but had no measurable effect on the pattern reversal visual evoked potential or alpha rhythm. Recent memory was significantly impaired, but assessment of digit span, reaction time, and distant memory showed no impairment. Physostigmine, an anticholinesterase, restored the P3 and reversed the recent memory impairment. These results strongly suggest a cholinergic role in generation of P3 potential and support the concept that P3 generation is related to memory processes.

Adult

Cognitive evoked potentials and disorders of recent memory.

P3 potentials evoked by spoken words were recorded from seven patients with disorders of recent memory and seven age-matched controls. Inclusion criteria included a clearly identifiable P3 to pure tone stimuli. Absence or marked decrement of P3 to word stimuli was seen in the patients even though they could perform the word task. The results are consistent with an encoding disorder and failure in elaboration of information processing.

Adult

Auditory P3 correlates of phonemic and semantic processing.

Auditory evoked potentials were recorded in twelve healthy subjects using phonemic and semantic word tasks. The late positive component (P3), analogous to tonal P300, varied as a function of cognitive task with increased latency and amplitude associated with semantic processing. These data are consistent with levels of processing theories in which semantic analysis is associated with a greater elaboration of stimulus evaluation.

Adult

Central cholinergic systems and the P3 evoked potential.

A cognitive evoked potential, the P3, is commonly altered in dementia states but little is known of the specific neuronal generators that are the source of this potential. Event-related evoked potentials and neuropsychological testing were obtained in six normal subjects during neuropharmacological manipulation of the central cholinergic system. Scopolamine (an anticholinergic) impaired recent memory, prolonged P3 latency and decreased P3 amplitude. These abnormalities were partially reversed by physostigmine (an anticholinesterase). The results imply that the cholinergic system is involved in the generation of the P3 potential.

Adult

Auditory brain-stem potentials with unilateral pontine hemorrhage.

Although there have been extensive anatomical and physiological studies in animals, the actual neural sources, or even the laterality, of some components of auditory brain-stem evoked potentials in humans are uncertain. We studied these responses in a 56-year-old patient who had a clearly demarcated pontine hemorrhage on the right side. The patient was somnolent, with dense left hemiplegia and signs of involvement of right cranial nerves V, VI, and VII. Stimulation of the left ear (ie, contralateral to the lesion) evoked a normal series of waves with clearly resolved positive components peaking at 2.0, 3.3, 4.8 (wave IV), and 6.0 ms (wave V). Stimulation of the right ear (ie, ipsilateral to the lesion) evoked only waves I, III, and IV. These results suggest that a pathway ipsilateral to the stimulated ear is necessary and sufficient for generation of auditory wave V and that wave IV is generated in bilateral pathways.

Cerebral Hemorrhage

Effects of gamma-vinyl-GABA on the human electroencephalogram.

Gamma-vinyl-GABA (GVG) is a new anticonvulsant drug that significantly raises the level of the gamma-aminobutyric acid in the brain (GABA). The effects of gamma-vinyl-GABA on the human electroencephalogram were studied to assess the role of GABAergic mechanisms on electrocortical activity. Serial EEGs were recorded in 15 epileptic patients undergoing a controlled clinical trial of gamma-vinyl-GABA. The effects of gamma-vinyl-GABA on alpha, beta, or theta activity, sleep spindles and epileptiform activity were studied. No changes could be detected in any of the intrinsic brain rhythms. Three patients showed a mild amelioration of epileptiform activity; no increase in epileptiform activity was seen.

Adult

Gamma-vinyl GABA.

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4-Aminobutyrate Transaminase

Effect of gamma-vinyl GABA on human pattern evoked visual potentials.

We studied the effects on human visual evoked potentials of gamma-vinyl GABA, an anticonvulsant drug that increases cerebral levels of gamma-aminobutyric acid. The subjects were 15 epileptic patients undergoing a clinical trial of this drug. Serial recordings were made from each patient periodically for 1 year. The stimulus was a reversing checkerboard pattern with a check size of 50 minutes. Plasma levels of other antiepileptic medications remained constant throughout the study. No changes, other than a normal variation of +/- 5 msec, were observed in peak latency throughout the study. These results indicate that there are no GABA-ergic effects on the P100 component evoked by large checkerboard pattern-reversal.

Adult